Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Malaria Journal
Published in: Malaria Journal 1/2013

Open Access 01-12-2013 | Case study

Experience and challenges from clinical trials with malaria vaccines in Africa

Authors: Grace Mwangoka, Bernhards Ogutu, Beverly Msambichaka, Tutu Mzee, Nahya Salim, Shubis Kafuruki, Maxmillian Mpina, Seif Shekalaghe, Marcel Tanner, Salim Abdulla

Published in: Malaria Journal | Issue 1/2013

Login to get access

Abstract

Malaria vaccines are considered amongst the most important modalities for potential elimination of malaria disease and transmission. Research and development in this field has been an area of intense effort by many groups over the last few decades. Despite this, there is currently no licensed malaria vaccine. Researchers, clinical trialists and vaccine developers have been working on many approached to make malaria vaccine available.
African research institutions have developed and demonstrated a great capacity to undertake clinical trials in accordance to the International Conference on Harmonization-Good Clinical Practice (ICH-GCP) standards in the last decade; particularly in the field of malaria vaccines and anti-malarial drugs. This capacity is a result of networking among African scientists in collaboration with other partners; this has traversed both clinical trials and malaria control programmes as part of the Global Malaria Action Plan (GMAP). GMAP outlined and support global strategies toward the elimination and eradication of malaria in many areas, translating in reduction in public health burden, especially for African children. In the sub-Saharan region the capacity to undertake more clinical trials remains small in comparison to the actual need.
However, sustainability of the already developed capacity is essential and crucial for the evaluation of different interventions and diagnostic tools/strategies for other diseases like TB, HIV, neglected tropical diseases and non-communicable diseases. There is urgent need for innovative mechanisms for the sustainability and expansion of the capacity in clinical trials in sub-Saharan Africa as the catalyst for health improvement and maintained.
Literature
1.
2.
Roca-Feltrer A, Carneiro I, Armstrong-Schellenberg JR: Estimates of the burden of malaria morbidity in Africa in children under the age of 5 years. Trop Med Int Health. 2008, 13: 771-783. 10.1111/j.1365-3156.2008.02076.x.CrossRefPubMed
3.
Rogerson SJ: Malaria in pregnancy and the newborn. Adv Exp Med Biol. 2010, 659: 139-152. 10.1007/978-1-4419-0981-7_12.CrossRefPubMed
4.
5.
6.
7.
Agnandji ST, Lell B, Soulanoudjingar SS, Fernandes JF, Abossolo BP, Conzelmann C, Methogo BG, Doucka Y, Flamen A, Mordmüller B, Issifou S, Kremsner PG, Sacarlal J, Aide P, Lanaspa M, Aponte JJ, Nhamuave A, Quelhas D, Bassat Q, Mandjate S, Macete E, Alonso P, Abdulla S, Salim N, Juma O, Shomari M, Shubis K, Machera F, Hamad AS, Minja R, RTS,S Clinical Trials Partnership: First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med. 2011, 365: 1863-1875.CrossRefPubMed
8.
Agnandji ST, Lell B, Fernandes JF, Abossolo BP, Methogo BG, Kabwende AL, Adegnika AA, Mordmüller B, Issifou S, Kremsner PG, Sacarlal J, Aide P, Lanaspa M, Aponte JJ, Machevo S, Acacio S, Bulo H, Sigauque B, Macete E, Alonso P, Abdulla S, Salim N, Minja R, Mpina M, Ahmed S, Ali AM, Mtoro AT, Hamad AS, Mutani P, Tanner M, RTS: A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N Engl J Med. 2012, 367: 2284-2295.CrossRefPubMed
9.
10.
Chilengi R: Clinical development of malaria vaccines: should earlier trials be done in malaria endemic countries?. Hum Vaccin. 2009, 5: 627-CrossRefPubMed
11.
Alonso PL: Malaria: deploying a candidate vaccine (RTS, S/AS02A) for an old scourge of humankind. Int Microbiol. 2006, 9: 83-93.PubMed
12.
Girad MP, Reed ZH, Friede M, Kieny MP: A review of human vaccine research and development: malaria. Vaccine. 2007, 25: 1567-1580. 10.1016/j.vaccine.2006.09.074.CrossRef
13.
Hill AVS: Pre-erythrocytic malaria vaccines:towards greater efficacy. Nat Rev Immunol. 2006, 6: 21-32. 10.1038/nri1746.CrossRefPubMed
14.
Peduzzi E, Westerfeld N, Zurbriggen R, Pluschke G, Daubenberger CA: Contribution of influenza immunity and virosomal-formulated synthetic peptide to cellular immune responses in a phase I subunit malaria vaccine trial. Clin Immunol. 2008, 127: 188-197. 10.1016/j.clim.2008.01.012.CrossRefPubMed
15.
Holder AA, Guevara Patino JA, Uthaipibull C, Syed SE, Ling IT, Scott-Finnigan T, Blackman MJ: Merozoite surface protein 1, immune evasion, and vaccines against asexual blood stage malaria. Parassitologia. 1999, 41: 409-414.PubMed
16.
Bouharoun-Tayoun H Druilhe P: Antibodies in falciparum malaria: what matters most, quantity or quality?. Mem Inst Oswaldo Cruz 87 Suppl. 1992, 3: 229-234.CrossRef
17.
Bouharoun-Tayoun H, Attanath P, Sabchareon A, Chongsuphajaisiddhi T, Druilhe P: Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes. J Exp Med. 1990, 172: 1633-1641. 10.1084/jem.172.6.1633.CrossRefPubMed
18.
Roussilhon C, Oeuvray C, Muller-Graf C, Tall A, Rogier C, Trape JF, Theisen M, Balde A, Perignon JL, Druilhe P: Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3. PLoS Med. 2007, 4: e320-10.1371/journal.pmed.0040320.PubMedCentralCrossRefPubMed
19.
Ndungu FM, Bull PC, Ross A, BS Lowe BS, Kabiru E, Marsh K: Naturally acquired immunoglobulin (Ig)G subclass antibodies to crude asexual Plasmodium falciparum lysates: evidence for association with protection for IgG1 and disease for IgG2. Parasite Immunol. 2002, 24: 77-82. 10.1046/j.0141-9838.2001.00440.x.CrossRefPubMed
20.
Chumpitazi BF, Lepers JP, Simon J, Deloron P: IgG1 and IgG2 antibody responses to Plasmodium falciparum exoantigens correlate inversely and positively, respectively, to the number of malaria attacks. FEMS Immunol Med Microbiol. 1999, 14: 151-158.CrossRef
21.
Luty AJ, Mayombo J, Lekoulou F, Mshana R: Immunologic responses to soluble exoantigens of Plasmodium falciparum in Gabonese children exposed to continuous intense infection. AmJTrop Med Hyg. 1994, 51: 720-729.
22.
Sarthou JL, Angel G, Aribot G, Rogier C, Dieye A, Toure BA, Diatta B, Seignot P, Roussilhon C: Prognostic value of anti-Plasmodium falciparum-specific immunoglobulin G3, cytokines, and their soluble receptors in West African patients with severe malaria. Infect Immun. 1997, 65: 3271-3276.PubMedCentralPubMed
23.
Shi YP, Sayed U, Qari SH, Roberts JM, Udhayakumar V, Oloo AJ, Hawley WA, Kaslow DC, Nahlen BL, Lal AA: Natural immune response to the C-terminal 19-kilodalton domain of Plasmodium falciparum merozoite surface protein 1. Infect Immun. 1996, 64: 2716-2723.PubMedCentralPubMed
24.
Taylor RR, Allen SJ, Greenwood BM, Riley EM: IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria. AmJTrop Med Hyg. 1998, 58: 406-413.
25.
Iriemenam NC, Khirelsied AH, Nasr A, ElGhazali G, Giha HA, Elhassan A-E, Agab-Aldour AA, Montgomery SM, Anders RF, Theisen M, Troye-Blomberg M, Elbashir MI, Berzins K: Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan. Vaccine. 2009, 27: 62-71. 10.1016/j.vaccine.2008.10.025.CrossRefPubMed
26.
Nebie I, Diarra A, Ouedraogo A, Soulama I, Bougouma EC, Tiono AB, Konate AT, Chilengi R, Theisen M, Dodoo D, Remarque E, Bosomprah S, Milligan P, Sirima SB: Humoral responses to Plasmodium falciparum blood-stage antigens and association with incidence of clinical malaria in children living in an area of seasonal malaria transmission in Burkina Faso, West Africa. Infect Immun. 2008, 76: 759-766. 10.1128/IAI.01147-07.PubMedCentralCrossRefPubMed
27.
Ndungu FM, Mwacharo J, Kimani D, Kai O, Moris P, Jongert E, Vekemans J, Olotu A, Bejon P: A statistical interaction between circumsporozoite protein-specific T cell and antibody responses and risk of clinical malaria episodes following vaccination with RTS,S/AS01E. PLoS One. 2012, 7: e52870-10.1371/journal.pone.0052870.PubMedCentralCrossRefPubMed
28.
Kester KE, Cummings JF, Ofori-Anyinam O, Ockenhouse CF, Krzych U, Moris P, Schwenk R, Nielsen RA, Debebe Z, Pinelis E, Juompan L, Williams J, Dowler M, Stewart VA, Wirtz RA, Dubois MC, Lievens M, Cohen J, Ballou WR, Heppner DG: Randomized, double-blind, phase 2a trial of falciparum malaria vaccines RTS, S/AS01B and RTS, S/AS02A in malaria-naive adults: safety, efficacy, and immunologic associates of protection. J Infect Dis. 2009, 200: 337-346. 10.1086/600120.CrossRefPubMed
29.
Kester KE, McKinney DA, Tornieporth N, Ockenhouse CF, Heppner DG, Hall T, Krzych U, Delchambre M, Voss G, Dowler MG, Palensky J, Wittes J, Cohen J, Ballou WR: Efficacy of recombinant circumsporozoite protein vaccine regimens against experimental Plasmodium falciparum malaria. J Infect Dis. 2001, 183: 640-647. 10.1086/318534.CrossRefPubMed
30.
Guinovart C, Aponte JJ, Sacarlal J, Aide P, Leach A, Bassat Q, Macete E, Dobaño C, Lievens M, Loucq C, Ballou WR, Cohen J, Alonso PL: Insights into long-lasting protection induced by RTS, S/AS02A malaria vaccine: further results from a phase IIb trial in Mozambican children. PLoS One. 2009, 4: e5165-10.1371/journal.pone.0005165.PubMedCentralCrossRefPubMed
31.
Olotu A, Moris P, Mwacharo J, Vekemans J, Kimani D, Janssens M, Kai O, Jongert E, Lievens M, Leach A, Villafana T, Savarese B, Marsh K, Cohen J, Bejon P: Circumsporozoite-specific T cell responses in children vaccinated with RTS, S/AS01E and protection against P. falciparum clinical malaria. PLoS One. 2011, 6: e25786-10.1371/journal.pone.0025786.PubMedCentralCrossRefPubMed
32.
Asante KP, Abdulla S, Agnandji S, Lyimo J, Vekemans J, Soulanoudjingar S, Owusu R, Shomari M, Leach A, Jongert E, Salim N, Fernandes JF, Dosoo D, Chikawe M, Issifou S, Osei-Kwakye K, Lievens M, Paricek M, Moller T, Apanga S, Mwangoka G, Dubois MC, Madi T, Kwara E, Minja R, Hounkpatin AB, Boahen O, Kayan K, Adjei G, Chandramohan D, Carter T: Safety and efficacy of the RTS, S/AS01(E) candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial. Lancet Infect Dis. 2011, 11: 741-749. 10.1016/S1473-3099(11)70100-1.CrossRefPubMed
33.
Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Milman J, Mandomando I, Spiessens B, Guinovart C, Espasa M, Bassat Q, Aide P, Ofori-Anyinam O, Navia MM, Corachan S, Ceuppens M, Dubois MC, Demoitie MA, Dubovsky F, Menendez C, Tornieporth N, Ballou WR, Thompson R, Cohen J: Efficacy of the RTS, S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet. 2004, 364: 1411-1420. 10.1016/S0140-6736(04)17223-1.CrossRefPubMed
34.
Casares S, Brumeanu TD, Richie TL: The RTS, S malaria vaccine. Vaccine. 2010, 28: 4880-4888. 10.1016/j.vaccine.2010.05.033.CrossRefPubMed
35.
36.
Schwartz L, Brown GV, Genton B, Moorthy VS: A review of malaria vaccine clinical projects based on the WHO rainbow table. Malar J. 2012, 11: 11-10.1186/1475-2875-11-11.PubMedCentralCrossRefPubMed
37.
Thompson FM, Porter DW, Okitsu SL, Westerfeld N, Vogel D, Todryk S, Poulton I, Correa S, Hutchings C, Berthoud T, Dunachie S, Andrews L, Williams JL, Sinden R, Gilbert SC, Pluschke G, Zurbriggen R, Hill AV: Evidence of blood stage efficacy with a virosomal malaria vaccine in a phase IIa clinical trial. PLoS One. 2008, 3: e1493-10.1371/journal.pone.0001493.PubMedCentralCrossRefPubMed
38.
Cech PG, Aebi T, Abdallah MS, Mpina M, Machunda EB, Westerfeld N, Stoffel SA, Zurbriggen R, Pluschke G, Tanner M, Daubenberger C, Genton B, Abdulla S: Virosome-formulated Plasmodium falciparum AMA-1 & CSP derived peptides as malaria vaccine: randomized phase 1b trial in semi-immune adults & children. PLoS One. 2011, 6: e22273-10.1371/journal.pone.0022273.PubMedCentralCrossRefPubMed
39.
Hoffman SL, Billingsley PF, James E, Richman A, Loyevsky M, Li T, Chakravarty S, Gunasekera A, Chattopadhyay R, Li M, Stafford R, Ahumada A, Epstein JE, Sedegah M, Reyes S, Richie TL, Lyke KE, Edelman R, Laurens MB, Plowe CV, Sim BK: Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria. Hum Vaccin. 2010, 6: 97-106. 10.4161/hv.6.1.10396.CrossRefPubMed
40.
Roestenberg M, McCall M, Hopman J, Wiersma J, Luty AJ, van Gemert GJ, Teelen K, Arens T, Spaarman L, Roeffen W, Snounou G, Renia L, Hermsen CC, Sauerwein R, d van V: Protection against a malaria challenge by sporozoite inoculation. N Engl J Med. 2009, 361: 468-477. 10.1056/NEJMoa0805832.CrossRefPubMed
41.
Roestenberg M, Teirlinck AC, McCall MB, Teelen K, Makamdop KN, Wiersma J, Arens T, Beckers P, van Gemert G, van de Vegte-Bolmer M, van der Ven AJ, Luty AJ, Hermsen CC, Sauerwein RW: Long-term protection against malaria after experimental sporozoite inoculation: an open-label follow-up study. Lancet. 2011, 377: 1770-1776. 10.1016/S0140-6736(11)60360-7.CrossRefPubMed
42.
Miura K, Keister DB, Muratova OV, Sattabongkot J, Long CA, Saul A: Transmission-blocking activity induced by malaria vaccine candidates Pfs25/Pvs25 is a direct and predictable function of antibody titer. Malar J. 2007, 6: 107-10.1186/1475-2875-6-107.PubMedCentralCrossRefPubMed
43.
Moorthy V, Reed Z, Smith PG: Measurement of malaria vaccine efficacy in phase III trials: report of a WHO consultation. Vaccine. 2007, 25: 5115-5123. 10.1016/j.vaccine.2007.01.085.CrossRefPubMed
44.
Swysen C, Vekemans J, Bruls M, Oyakhirome S, Drakeley C, Kremsner P, Greenwood B, Ofori-Anyinam O, Okech B, Villafana T, Carter T, Savarese B, Duse A, Reijman A, Ingram C, Frean J, Ogutu B: Development of standardized laboratory methods and quality processes for a phase III study of the RTS, S/AS01 candidate malaria vaccine. Malar J. 2011, 10: 223-10.1186/1475-2875-10-223.PubMedCentralCrossRefPubMed
45.
Smith T, Schellenberg JA, Hayes R: Attributable fraction estimates and case definitions for malaria in endemic areas. Stat Med. 1994, 13: 2345-2358. 10.1002/sim.4780132206.CrossRefPubMed
46.
Moonen B, Cohen JM, Snow RW, Slutsker L, Drakeley C, Smith DL, Abeyasinghe RR, Rodriguez MH, Maharaj R, Tanner M, Targett G: Operational strategies to achieve and maintain malaria elimination. Lancet. 2010, 376: 1592-1603. 10.1016/S0140-6736(10)61269-X.PubMedCentralCrossRefPubMed
47.
Alonso PL, Brown G, Arevalo-Herrera M, Binka F, Chitnis C, Collins F, Doumbo OK, Greenwood B, Hall BF, MM Levine MM, Mendis K, Newman RD, Plowe CV, Rodriguez MH, Sinden R, Slutsker L, Tanner M: A research agenda to underpin malaria eradication. PLoS Med. 2011, 8: e1000406-10.1371/journal.pmed.1000406.PubMedCentralCrossRefPubMed
48.
Smith T, Killeen G, Lengeler C, Tanner M: Relationships between the outcome of Plasmodium falciparum infection and the intensity of transmission in Africa. AmJTrop Med Hyg. 2004, 71: 80-86.
49.
Smith T, Maire N, Dietz K, Killeen GF, Vounatsou P, Molineaux L, Tanner M: Relationship between the entomologic inoculation rate and the force of infection for Plasmodium falciparum malaria. AmJTrop Med Hyg. 2006, 75: 11-18.
50.
Smits HL, Leatherman S, Berwick DM: Quality improvement in the developing world. Int J Qual Health Care. 2002, 14: 439-440. 10.1093/intqhc/14.6.439.CrossRefPubMed
51.
Gardette V, Coley N, Toulza O, Andrieu S: Attrition in geriatric research: how important is it and how should it be dealt with?. J Nutr Health Aging. 2007, 11: 265-268.PubMed
52.
Eakin, Bull SS, Riley K,Reeves MM, Gutierrez S, McLaughlin P: Recruitment and retention of Latinos in a primary care-based physical activity and diet trial: The Resources for Health study. Health Educ Res. 2007, 22: 361-371.PubMed
53.
Doumbo OK: Global voices of science. It takes a village: medical research and ethics in Mali. Science. 2005, 307: 679-681. 10.1126/science.1109773.CrossRefPubMed
54.
Diallo DA, Doumbo OK, Plowe CV, Wellems TE, Emanuel EJ, Hurst SA: Community permission for medical research in developing countries. Clin Infect Dis. 2005, 41: 255-259. 10.1086/430707.CrossRefPubMed
55.
Chokshi DA, Thera MA, Parker M, Diakite M, Makani J, Kwiatkowski DP, Doumbo OK: Valid consent for genomic epidemiology in developing countries. PLoS Med. 2007, 4: e95-10.1371/journal.pmed.0040095.PubMedCentralCrossRefPubMed
56.
Tindana PO, Singh JA, Tracy CS, Upshur RE, Daar AS, Singer PA, Frohlich J, Lavery JV: Grand challenges in global health: community engagement in research in developing countries. PLoS Med. 2007, 4: e273-10.1371/journal.pmed.0040273.PubMedCentralCrossRefPubMed
57.
Shubis K, Juma O, Sharifu R, Burgess B, Abdulla S: Challenges of establishing a Community Advisory Board (CAB) in a low-income, low-resource setting: experiences from Bagamoyo. Tanzania. Health Res Policy Syst. 2009, 7: 16-10.1186/1478-4505-7-16.PubMedCentralCrossRefPubMed
58.
59.
Nyika A, Chilengi R, Ishengoma D, Mtenga S, Thera MA, Sissoko MS, Lusingu J, Tiono AB, Doumbo O, Sirima SB, Lemnge M, Kilama WL: Engaging diverse communities participating in clinical trials: case examples from across Africa. Malar J. 2010, 9: 86-10.1186/1475-2875-9-86.PubMedCentralCrossRefPubMed
60.
61.
62.
63.
Lang TA, White NJ, Tran HT, Farrar JJ, Day NP, Fitzpatrick R, Angus BJ, Denis E, Merson L, Cheah PY, Chilengi R, Kimutai R, Marsh K: Clinical research in resource-limited settings: enhancing research capacity and working together to make trials less complicated. PLoS Negl Tro. Dis. 2010, 4: e619-10.1371/journal.pntd.0000619.CrossRef
64.
65.
Metadata
Title
Experience and challenges from clinical trials with malaria vaccines in Africa
Authors
Grace Mwangoka
Bernhards Ogutu
Beverly Msambichaka
Tutu Mzee
Nahya Salim
Shubis Kafuruki
Maxmillian Mpina
Seif Shekalaghe
Marcel Tanner
Salim Abdulla
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2013
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-12-86

Other articles of this Issue 1/2013

Malaria Journal 1/2013 Go to the issue

Research

Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria

Research

Inter-observer agreement according to malaria parasite density

Research

High frequency of the erythroid silent Duffy antigen genotype and lack of Plasmodium vivax infections in Haiti

Research

Limitations of microscopy to differentiate Plasmodium species in a region co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi

Research

Accurate identification of the six human Plasmodium spp. causing imported malaria, including Plasmodium ovale wallikeri and Plasmodium knowlesi

Research

Clinical relevance of different biomarkers in imported plasmodium falciparum malaria in adults: a case control study

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24 to hear Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits